Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain–Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV infection are globally underway, but Food and Drug Administration (FDA)-approved treatments are not available yet. Compounds from Chinese medicinal herbs may offer an opportunity for potential therapies for anti-ZIKV infection. In this study, we evaluated the antiviral efficacy of harringtonine against ZIKV. Harringtonine possessed anti-ZIKV properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection. The antiviral activity also observed in the treatment against Japanese encephalitis reporter virus (RP9-GFP strain). Overall, this study demonstrated that harringtonine would be a favorable potential candidate for the development of anti-ZIKV infection therapies.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) can cause permanent neurological damage and death, yet no approved drugs exist for these infections. Rhodiola crenulate, an herb used in traditional Chinese medicine for its antioxidation and antifatigue properties, was studied for its antiviral activity against ZIKV and JEV in vitro. The cytotoxicity of Rhodiola crenulata extract (RCE) was evaluated using the CCK-8 reagent. Antiviral effects of RCE were assessed in ZIKV-infected or JEV-infected Vero cells via quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, fluorescent focus assay (FFA), and immunofluorescence assay (IFA). The cell-free antiviral effects of RCE were evaluated using an inactivation assay. To determine the stage of the viral life cycle affected by RCE, time-of-addition, binding, and entry assays were conducted. Three bioactive constituents of RCE (salidroside, tyrosol, and gallic acid) were tested for antiviral activity. RCE exhibited dose-dependent anti-ZIKV and anti-JEV activities at non-cytotoxic concentrations, which were likely achieved by disrupting viral binding and stability. Gallic acid exhibited antiviral activity against ZIKV and JEV. Our findings indicate that RCE disrupts viral binding and stability, presenting a potential strategy to treat ZIKV and JEV infections.

Cisplatin (cis-diamminedichloroplatinum(II) [DDP]) is a key chemotherapeutic agent for advanced endometrial cancer; however, chemoresistance substantially limits its clinical benefit. Extracellular vesicles (EVs) mediate intercellular communication and influence tumour cell behaviour and therapeutic response. We investigated whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) and natural killer cell-derived extracellular vesicles (NK-EVs) modulate cisplatin responsiveness in endometrial cancer cells (RL95-2 and HEC-1A). MSC-EVs and NK-EVs were isolated and characterised using nanoparticle tracking analysis, scanning electron microscopy, and EV marker profiling. MSC-EVs and NK-EVs reduced RL95-2 and HEC-1A cell viability in a dose-dependent manner, with MSC-EVs exhibiting substantial effects at lower particle concentrations. In a cisplatin-resistant HEC-1A (HEC-1A DDP-R) model, MSC-EVs were associated with greater reductions in cell viability under cisplatin treatment conditions, whereas NK-EVs showed comparatively modest effects. Mechanistic analyses demonstrated altered expression of apoptosis- and cell cycle–related proteins, including increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels and reduced cyclin A and cyclin D1 expression following MSC-EV treatment. Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry demonstrated increased apoptotic cell populations after MSC-EV treatment, with MSC-EV + DDP co-treatment resulting in the highest apoptotic fraction in chemoresistant HEC-1A cells. Collectively, these findings indicate that MSC-EVs are associated with altered cellular responses to cisplatin in chemoresistant endometrial cancer cells, accompanied by changes in apoptosis-related protein expression, apoptotic cell populations, and cell-cycle regulators. Further investigation is required to determine their mechanistic role and therapeutic potential in overcoming chemoresistance.